Bacterial polysaccharides have been shown to be effective immunogens for use in vaccines, particularly when conjugated to a carrier protein. Commercial conjugate vaccines are available against Haemophilus influenzae type b (Hibtiter® Wyeth-Lederle), pneumococcal polysaccharides (Prevnar®—Wyeth-Lederle) and meningococcal polysaccharides (Meningitec®—Wyeth-Lederle and Menactra®—Sanofi).
Immunogenic compositions and vaccines comprising a Hib conjugate, a N. meningitidis saccharide conjugate, whole cell pertussis and hepatitis B surface antigen have also been described. For instance WO 02/00249 discloses a seven valent immunogenic composition comprising a diphtheria toxoid, tetanus toxoid, whole cell pertussis, Hepatitis B surface antigen, Hib conjugate, MenA conjugate and MenC conjugate. The clinical trial results presented use a 5 μg saccharide dose of each of the bacterial saccharide conjugates.
The present invention concerns the provision of a combination vaccine comprising a Hib conjugate, an additional bacterial saccharide conjugate (for example an N. meningitidis saccharide conjugate) and further antigens including one or both of whole cell pertussis and Hepatitis B surface antigen. The saccharide doses used allow a good immune response to be generated against Hib and the additional bacterial saccharides as well as against the pertussis component and/or the Hepatitis B surface antigen component.
The inventors have surprisingly found that by reducing the saccharide dose of Hib and/or additional bacterial conjugates to below 5 μg per dose, in a combination vaccine comprising whole cell pertussis and/or Hepatitis B surface antigen, a good immune response to the saccharide conjugates is maintained and the immunogenicity of whole cell pertussis and Hepatitis B surface antigen is enhanced (for example such that the GMC for Pw and/or Hepatitis B as measured by ELISA is higher than the level achieved after immunisation with an immunogenic composition containing a 5 μg saccharide dose of each conjugate).
Accordingly, a first aspect of the invention provides an immunogenic composition comprising a Hib saccharide conjugate, at least one additional bacterial saccharide conjugate(s), and a further antigen selected from the group consisting of whole cell pertussis and hepatitis B surface antigen, wherein the saccharide dose of the Hib saccharide conjugate is less than 5 μg per dose.